Stanton R. Mehr, President, SM Health Communications LLC
Consider the following hypothetical scenario: A new infliximab biosimilar is approved for use in patients with rheumatoid arthritis and Crohn’s disease. Nine months after its introduction, an unexpected safety problem is revealed in 8% of patients—severe vestibular dysfunction, resulting in disabling imbalance and dizziness. How would this adverse effect be linked with the new drug and how quickly would this link be established? That may be dependent on how the drug is identified (with the same or different nonproprietary name as the innovator) and the capability of the adverse effect reporting system. It is one thing to monitor for side effects associated with the reference drug, but it is quite another to be able to identify something that is entirely new.
In November 2013, the Academy of Managed Care Pharmacy hosted a Task Force conference discussing the highly anticipated approval process for new biosimilar agents and how to monitor their safety and efficacy. The results of this Task Force was published January 2015 the Journal of Managed Care and SpecialtyPharmacy.
The Food and Drug Administration (FDA) was charged by Congress with implementing the pathway to approval, called the 351(k) pathway. Over the years, the FDA has been cautious about releasing details of the biosimilar regulations; many in the United States (including clinicians and manufacturers of innovator products) are concerned about the efficacy and safety of biosimilars, which are not simply generic copies of their biologics. The experience of the European Medicines Agency may be instructive here: Since 2007, it has approved several biosimilars, including versions of filgrastim, epoetin, infliximab, and follitropin, without any significant red flags in terms of safety or efficacy. This extensive clinical use of biosimilars in Europe does not erase all concerns about these agents, however.
There is no shortage of expensive biologics whose patents have expired or are near expiration. An unpublished analysis from Express Scripts estimated that the introduction of biosimilars for 11 biologic agents whose patents have expired could result in more than $250 billion savings for the US health system over 10 years. Two important caveats to this estimate are (1) this analysis is was based on 30% savings per prescription (today, this is more conservative, at 15% to 20%, according to our market research) and (2) it does not consider the potential costs of any new and unforeseen adverse drug events (ADEs) resulting from the use of new biosimilars. However, the second point is of more relevance to this discussion.
Biosimilars are not exact copies of the innovator, or reference, agent. Biologics are complex proteins, and differences in manufacturing processes alone are enough to result in unique physical structures—for example, a new fold in the molecule may occur, which may expose more or less of its surface to target cell receptors. It may also result in slightly different chemical structures, such as glycation, which may not result in clinical differences. Does this mean that biosimilars are as efficacious and have the same safety profile as the reference medications? Although the ordinary use of biologics like TNF-alpha inhibitors in practice cannot exactly be called safe, the experience accumulated over more than a decade has provided a solid picture of their safety profiles.
The 351(k) pathway does not require large-scale clinical trial programs to prove that the use of a biosimilar results in the same outcomes as the innovator product, so we may not have full confidence that the biosimilar agent performs exactly the same way that the innovator drug does. For this reason, policy experts cite the need for a mechanism to evaluate real-world outcomes with newly approved biosimilar agents, including a method of collecting data on the long-term use of these biologics. This effort would also be helpful to validate biosimilars’ effectiveness compared with their reference products.
The Task Force’s recommendations may start the ball rolling to establish a mechanism for how this postmarketing surveillance will be performed, who will coordinate it, and how any results or safety signals will be reported. I suggest you read the report. It opens a window onto the current pharmaceutical surveillance system and raises important questions.
SM Health Communications provides writing, consulting, and innovative market research services for the payer markets. Its proprietary P&T Insight™ virtual P&T Committee program is the leading mock P&T Committee product in the field. We’ve participated in many market research projects involving biosimilar development and launch, from the point of view of the biosimilar and the innovator drug manufacturer. For more information, please visit www.smhealthcom.com or contact Stanton R. Mehr, President, at firstname.lastname@example.org.